Phosphodiesterases (PDEs) are a class of enzymes that degrade second messengers cyclic AMP (cAMP) and cyclic GMP (cGMP) in the body. To date, eleven families of PDEs (PDE1 to PDE11) have been identified with each family having specificity for cAMP or cGMP or both. The tissue distribution of each PDE family varies from tissue to tissue: It is believed that the cellular reactions in different organs are controlled by different PDE families.
A number of PDE inhibitors have been developed. Examples include PDE3 inhibitors that are intended for the treatment of angina pectoris, heart failure and hypertension and serve as antiplatelet and antiasthmatic agents; PDE4 inhibitors that are intended for the treatment of asthma, chronic obstructive pulmonary disease (COPD), interstitial pneumonia, allergic rhinitis, atopic dermatitis, rheumatoid arthritis, multiple sclerosis, Crohn's disease, inflammatory colitis, Alzheimer's disease, dementia, Parkinson's disease and depression; and PDE5 inhibitors that are already in clinical use as a treatment for erectile dysfunction. A recent study reports that minocycline, a PDE10A modulator, has proven effective in patients with Huntington's disease (Patent Document 1). Also, a patent application describes PDE10 inhibitors as an effective cure for Huntington's disease, Alzheimer's disease, dementia, Parkinson's disease, schizophrenia and other psychiatric disorders (Patent Document 2).
While some pyrazolopyridine pyridazinone derivatives have been described as PDE inhibitors (Patent Documents 3 and 4), no literature exists that describes compounds that have the same characteristic structure as the compounds of the present invention: a pyridazinone ring linked to position 4 of a pyrazolopyridine ring. Certain compounds that have a pyrazolopyridine ring substituted at position 3 with a dihydropyrydazinone group and a pyridazinone group have been reported to serve as adenosine antagonists (Patent Documents 5, 6, 7 and 8). Their structure, however, is apparently different from that of the compounds of the present invention, in which the pyridazinone group is linked to position 4 of pyrazolopyridine ring.
A pyrazolopyridine derivative that acts as a bronchodilator has also been described (Patent Document 9). Nevertheless, none of the above-described compounds share the structural feature of the compounds of the present invention.    Patent Document 1 WO01024781 Pamphlet    Patent Document 2 Japanese Patent Laid-Open Publication No. 2002-363103    Patent Document 3 Domestic re-publication of PCT application No. WO98/14448    Patent Document 4 Japanese Patent Laid-Open Publication No. Hei 10-109988    Patent Document 5 Japanese Patent Laid-Open Publication No. Hei 2-243689    Patent Document 6 Japanese Patent Laid-Open Publication No. Hei 4-253987    Patent Document 7 WO02018382 Pamphlet    Patent Document 8 WO03004494 Pamphlet    Patent Document 9 Japanese Patent Laid-Open Publication No. Hei 8-12673